Abstract:
:Adaptation to low oxygen conditions is essential for maintaining homeostasis and viability in oxygen-consuming multi-cellular tissues, including solid tumors. Central in these processes are the hypoxia-inducible transcription factors, HIF-1 and HIF-2, controlling genes involved in e.g. glucose metabolism and neovascularization. Tumor hypoxia and HIF expression have also been associated with a dedifferentiated phenotype and increased aggressiveness. In this report we show that the MAX interactor-1 (MXI1) gene is directly regulated by HIF proteins in neuroblastoma and breast cancer cells. HIF-binding and transactivation were detected within MXI1 gene regulatory sequences in the vicinity of the MXI1-0 promoter, leading to rapid induction of the alternate MXI1-0 isoform followed by a long-term induction of both the MXI1-0 and MXI1 isoforms. Importantly, knock-down of MXI1 had limited effect on MYC/MYCN activity under hypoxia, an observation that might be related to the different functional attributes of the two MXI1 isoforms.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Löfstedt T,Fredlund E,Noguera R,Navarro S,Holmquist-Mengelbier L,Beckman S,Påhlman S,Axelson Hdoi
10.1016/j.yexcr.2009.02.015subject
Has Abstractpub_date
2009-07-01 00:00:00pages
1924-36issue
11eissn
0014-4827issn
1090-2422pii
S0014-4827(09)00079-2journal_volume
315pub_type
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